# Cyproheptadine

Category: Drugs & Compounds

Also known as: Periactin

Cyproheptadine is a first-generation antihistamine that functions as a non-selective serotonin antagonist, and Ray Peat considered it a uniquely systemic tool for removing the brakes on metabolic rate. Originally developed as an anti-allergy drug in the tricyclic class, it was…

10 passages · 3 authors · 2014–2025 · Most-cited: [Ray Peat](https://bioenergeticoracle.com/md/voices/ray-peat/index.md)

Canonical page: https://bioenergeticoracle.com/concepts/cyproheptadine

## Synthesis

**Cyproheptadine** is a first-generation antihistamine that functions as a *non-selective serotonin antagonist*, and Ray Peat considered it a uniquely systemic tool for removing the brakes on metabolic rate. [Source 1, 5] Originally developed as an anti-allergy drug in the tricyclic class, it was subsequently discovered to block serotonin receptors, and Dinkov notes it also possesses **anticholinergic** properties, blocking the receptors through which estradiol mediates its pro-inflammatory and growth-promoting effects. [Source 1] By antagonizing histamine, serotonin, and acetylcholine simultaneously, cyproheptadine renders estrogen much more benign and directly addresses the mediators of stress-induced metabolic suppression. [Source 1, 5]

Peat emphasized that cyproheptadine is effective for insomnia, irritable bowel syndrome (IBS), and nocturnal episodes of asthma or epilepsy-like conditions, but he consistently warned that dosing must begin extremely low. [Source 2, 9] He recommended starting with **half a milligram to one milligram** at bedtime to judge sensitivity, as even 4 mg can make some people too torpid to function the next morning. [Source 7, 9] Roddy relayed that Peat considered 4 mg a substantial dose, and that individuals who tolerate 16 mg or more without sedation likely have an intestine producing a *massive amount of serotonin and histamine*. [Source 3] Peat noted that the drug’s effects can persist for days after symptoms stop, and that small amounts are safe for daily, long-term use. [Source 9, 10]

The drug’s mechanistic profile extends beyond receptor antagonism. Dinkov has written that cyproheptadine antagonizes **aldosterone**, giving it diuretic effects similar to spironolactone. [Source 4] Peat described it as opposing not only serotonin but also adrenaline, cortisol, estrogen, and TLR-4, while preventing soft tissue calcification. [Source 5] Dinkov added that drugs inhibiting serotonin synthesis are currently in clinical trials for morbid obesity and type 2 diabetes, causing rapid and sustainable weight loss without caloric restriction, and that cyproheptadine’s serotonin blockade achieves a comparable unleashing of metabolic rate. [Source 1] He also noted that most SSRI antidepressants actually raise **allopregnanolone** levels in the brain, and some doctors prescribe cyproheptadine alone as an antidepressant therapy, acting in opposition to the serotonergic properties of SSRIs. [Source 6]

Regarding specific cautions, Peat advised that thyroid and the dependent neurosteroids are the foundational regulators, with reactive adrenaline, serotonin, nitric oxide, and prostaglandins as the immediately involved factors in insomnia, and that keeping **endotoxin absorption** low through diet or antibiotics can often make a significant difference. [Source 2] Dinkov addressed a common warning against cyproheptadine use in benign prostatic hyperplasia (BPH), attributing it to high-dose anticholinergic urine retention rather than any direct harm to the prostate, and dismissed the peptic ulcer contraindication as contradictory since cyproheptadine blocks H2 receptors used to treat ulcers. [Source 8] Peat recommended no more than 2 mg daily due to potential liver issues, though studies in children with functional gastrointestinal disorders have used 4 mg or more. [Source 4] He also noted that combinations of coffee, aspirin, progesterone, thyroid, vitamin D, and calcium can usually achieve the same broad-spectrum goals as cyproheptadine without the side effect of weight gain. [Source 5]

## People also ask

### How does cyproheptadine increase metabolic rate?

Peat argued it removes metabolic brakes by simultaneously blocking serotonin, histamine, and acetylcholine, which are stress mediators that suppress energy production, while also opposing cortisol, estrogen, and aldosterone.

### Why does Peat recommend starting with a very low dose?

Peat warned that even 4 mg can cause excessive next-day sedation, so he advised beginning with half a milligram to one milligram at bedtime to assess individual sensitivity before increasing.

### Can cyproheptadine be used as an antidepressant?

The corpus notes that some doctors prescribe it alone for depression, acting in opposition to the serotonergic properties of SSRIs, which actually raise allopregnanolone levels in the brain.

## Related concepts

- [Anemia](https://bioenergeticoracle.com/md/concepts/anemia/index.md)
- [Biotin](https://bioenergeticoracle.com/md/concepts/biotin/index.md)
- [DMSO](https://bioenergeticoracle.com/md/concepts/dmso/index.md)
- [Hyperammonemia](https://bioenergeticoracle.com/md/concepts/hyperammonemia/index.md)

## Cited passages

Passage numbers match the `[Source N]` markers in the synthesis above.

### Source 1 — The Myths of Supplementation with Giorgi Dinkov

Georgi Dinkov · Interview · Oct 9, 2024 · https://www.youtube.com/watch?v=bHQnx-5PjFM

> **MomentumforLifeTV:** Yes, much more dangerous. And I know Georgi and I are not going out and saying drink heaps of coffee either way. You still need to have a functioning metabolism to be able to utilize the caffeine in the coffee, right? You need to have a full meal and have caffeine with a full meal. Yes, absolutely. not fasted, not on an empty stomach. This other thing, other one that I have found really fascinating over the last few years, and Tomo talked about it in a very early episode about sleep, and that's ciproheptadine, which is sold over the counter in Australia as periactin. Yep. Can you talk about ciproheptadine?
>
> **Georgi Dinkov:** They call it a non-selective serotonin antagonist. It was actually originally developed as an antihistamine, as an anti-allergy drug. And it belongs to a class of drugs called the tricyclids. And basically all of these drugs were found to block the serotonin receptors as well. So by taking cyproheptadine, not only you're blocking histamine, which is one of the mediators through which estrogen mediates its effects, the other one being acetylcholine, but you're also blocking serotonin. And by the way, cyproheptadine is also anticholinergic. It blocks the cholinergic receptors as well. So if you block the histamine receptors and if you block the cholinergic receptors, effectively estradiol, estrogen, becomes much more benign because most of the negative effects of estrogen on the body, on the tissue, especially its growth-promoting effects, and the pro-inflammatory effects are done through histamine and acetylcholine. And cyproheptadine happens to block both of these. It's pretty potent. Then they discovered a little bit later on, maybe about 10 years after it was invented, they discovered that cyproheptadine also blocks the serotonin receptors. And blocking serotonin is one of the cardinal, the most beneficial and most systemic in terms of effects ways to unleash, to remove the brakes on your metabolic rate. Drugs that inhibit the synthesis of serotonin are currently in clinical trials for both obesity, morbid obesity, and type 2 diabetes, and have so far been extremely successful in causing rapid, and I emphasize rapid and sustainable, weight loss in people that have a weight problem or a diabetes problem without changing calories. So if you want to eat all the food that you like without counting calories, without being on a diet, find a way to either lower your serotonin or block its effects with potentially chemicals like cyproheptadine.

### Source 2 — Ray Peat Email Advice Depository — Post 904

Ray Peat · Email · Dec 7, 2022

> ## Thread 2
>
> **Question:** Would it be safe to use more than 4 mg of cyproheptadine for insomnia and IBS? Someone mentioned I could use 16 mg. I found some studies that use these doses, but I have always seen you refer to the smaller doses, and was wondering what your reasoning was. Thanks.
>
> **Ray Peat:** I have known people who did well with 12 mg/day, and know that some people use much more, but until you know your sensitivity to it, it's best to start with the minimal doses. Even 4 mg at night can make some people too torpid to function the next morning.
>
> **Question:** I tried 12mg of cyproheptadine for a couple day. It made me feel and think differently, but didn't make me tired, or let me fall asleep. The day after, I was a little muted, but got more errands done than usual. Are high or low levels of serotonin responsible for a person's reaction to the drug? Or is insomnia always from an underenergized brain, from lack of thyroid?
>
> **Ray Peat:** I think thyroid and the dependent neurosteroids are the basic things, and that the reactive adrenaline, serotonin, nitric oxide, and prostaglandins are the immediately involved things. Keeping endotoxin absorption low can often make a big difference, with diet or antibiotics.

### Source 3 — Bioenergetic Helpline #4: White Tongue, Importance of T4, Sleep Issues, High-Dose K2, Antibiotics

Danny Roddy · Interview · Dec 20, 2025 · https://www.youtube.com/watch?v=sCYdXExlDFk

> **Danny Roddy:** Yeah. In the email wiki, I think somebody asked him, uh, Ray, what was the big dose? And I think he said, I hope I'm not butchering this, but I thought he said like, he, you wouldn't want to take over four milligrams or so. And that seemed like a, like a big dose. That was like a whole tablet of periactin. And then I talked to somebody a long time ago and they were taking like 16 milligrams and they didn't notice anything from it. And he was asking me about it. And I said, I didn't know. And he emailed Ray and Ray replied, like your intestine must be producing a massive amount of serotonin and histamine to be able to do that. Because normally if a person takes even four milligrams, they'll be knocked out. Like they'll be unconscious. Like, like, so. Anyways, but so if, if Ray is saying four milligrams is the max, like in my limited experience, some people even do well on like a fourth a milligram. So a really small amount. So, and then it seems to accumulate as you take it. And so if a person benefited from like one or two milligrams, and then that was like too much for them at like a week or two later, they may, they might have to lower it. But and then I, there's a paper about a girl taking 24 milligrams. And I think she has legitimate Cushing's disease and the doctor tries to take her off of it and all her symptoms come back. So I'm kind of contradicting myself here, but like I'd be a little bit nervous over four milligrams or so, but I guess there are situations where huge amounts could be valuable. Thanks. Jack, what's up?

### Source 4 — IdeaLabs Forum Q&A — Cyproheptadine

Georgi Dinkov · Forum Q&A · Dec 17, 2016

> **Georgi Dinkov:** (2019-01-18) Thanks so much for the feedback!
>
> **CaliforniaKat:** (2019-01-22) I'm sorry in advance to tag you. @haidut I'm wondering about the differences between cypro and Mirtazapine. Can my rat safely transition from one to the other? High adrenaline seems to be a problem that continues to get worse, even on 7.5 mg Mirt. Poor metabolic nd poor thyroid function, taking NDT but little else besides Estroban at 1/2 dose. Peat style diet since August. How the rat started Mirt is a long story but has been on it since June. I have purchased Cypro for my rat and it should arrive today or tomorrow. Would love your thoughts about dosing, transitioning, etc. Again, sorry to to tag without permission. Thanks so much.
>
> **Georgi Dinkov:** (2019-01-30) Molecularly they are similar but I think mirtazapine is agonist on 5-HT1 and also stronger antagonist on 5-HT3. Also, mirtazapine has a nasty side effect called QT prolongation. I personally prefer cypro. I think @DaveFoster has used mirtazapine so he may be able to shed more light on how it compares to cypro.
>
> **Kartoffel:** (2019-01-31) I have been using the cyproheptadine for a few days now and wanted to give a brief review/ share my experience with it. The first day I took two doses - 1mg in the afternoon and 1.5mg at night - and they knocked me out pretty well. I almost immediately fell asleep after the first dose, and the second caused me to sleep through the night for 12 hours. On the second day, I decided to limit it to one dose of 1mg at night, and I am doing really well with that, so far. The sense of pressure I had in my stomach for about a month disappeared, my appetite in the morning drastically increased, and I now wanna have a huge breakfast (usually can't eat much before the afternoon). I also dream more vividly, and the extreme tiredness I had during the day after the first try has not recurred. So, overall the cypro works really well for me. Much gracias to @haidut for providing it!

### Source 5 — Ray Peat Email Advice Depository — Post 326

Ray Peat · Email · Dec 31, 2016

> **Question:** You talk a lot about the benefit of anti-serotonin drugs, and cyproheptadine acts as an anti-serotonin, -adrenaline, -cortisol, -estrogen, -cholinergic, TLR-4 antagonist, opposes soft tissue calcification and the list goes on. I've taken it for about a year, and I noticed nothing but positives. Do you know of a substance comparable to cyproheptadine and the serotonin antagonists without weight gain as a side effect?
>
> **Ray Peat:** I don’t know of any specific thing like that, but combinations of things—coffee, aspirin , progesterone , thyroid, vitamin D, calcium, etc.—can usually achieve the same goals.

### Source 6 — IdeaLabs Forum Q&A — Cyproheptadine

Georgi Dinkov · Forum Q&A · Dec 17, 2016

> **Tarmander:** (2016-12-17) Fantastic Haidut. I've heard rumblings that in GB they are going to start regulating against the research chemicals loop hole. Have you heard anything about America Haidut?
>
> **Georgi Dinkov:** (2016-12-17) Have not heard anything yet but I would not be surprised if it happens as pharma companies revenue has been suffering lately. The problem is that it would be difficult to enforce without hurting the business of companies like Sigma Aldrich and such.
>
> **Arclight:** (2016-12-19) @haidut , any thoughts on taking this product while on SSRI-medications? Pro's or con's`?
>
> **Georgi Dinkov:** (2016-12-19) I would ask a doctor because cyproheptadine will probably act in a way opposite to the serotonergic properties of the SSRI drug. Most doctors seem believe that serotonin is an anti-depressant while in reality most SSRI drugs raise allopregnanolone levels in the brain and some of them are even partial serotonin antagonists. Some doctors even prescribe cyproheptadine alone as an antidepressant therapy so you can ask the doctor about maybe doing that.
>
> **keith:** (2016-12-27) @haidut, I know you could not recommend or endorse for your product to be used in this way, but theoretically speaking, are you able to share any thoughts about how effective cyproheptadine + DMSO might be as an emergency option for severe allergies such as bee stings? My wife has a bee sting allergy, but refuses to fill her epipen prescription on account of the cost. She carries a bottle of liquid benedryl with the intention of chugging it is she is ever stung. My understanding is that while it may help, the benedryl may not act fast enough in that type of situation. We have gotten conflicting information from doctors on this. Anyway, it seems like DMSO would significantly increase the absorption time, and I would think cyproheptadine would work as effectively as benedryl theoretically. Seems like it might be safer than epinephrine too. Thoughts?

### Source 7 — Cyproheptadine

Ray Peat · Email · 2015

> # Cyproheptadine
>
> [TOPICAL USE] It would be hard to regulate the dose via the skin.
>
> It's good to start with about half a milligram, at bedtime, to judge its effects when sedation isn't risky.
>
> [Jared: Dr. Peat, As a woman, I'm trying to figure out if nortriptyline (taken for IBS at 10 mg/day) could be exacerbating the IBS since it is most likely increasing serotonin. Would that be true? After having surgery to remove breast implants, I have had terrible neuropathy. Could that be serotonin and endotoxin related? What would be the most effective steps to heal the neuropathy? Thank you for your work. Warmly,]
>
> Surgical stress can result in prolonged hormonal imbalance, including low thyroid and high estrogen and serotonin. Have you had blood tests for thyroid and vitamin D, etc.? Have you tried cyproheptadine for the IBS?
>
> Expert Rev Gastroenterol Hepatol. 2010 Jun; 4(3): 293–304. Management of functional abdominal pain and irritable bowel syndrome in children and adolescents Eric Chiou1 and Samuel Nurko. ……………………..
> Cyproheptadine
> Cyproheptadine is a medication with multiple mechanisms, including antihistaminic, anticholinergic and antiserotonergic properties, as well as possible calcium channel blockade effects. It has been used in appetite stimulation and prevention of pain and vomiting in abdominal migraine and cyclic vomiting syndrome. Sadeghian et al. studied the use of cyproheptadine in 29 children and adolescents (aged 4.5–12 years) diagnosed with FAP in a 2-week, double-blind placebo-controlled trial. At the end of the study, 86% in the cyproheptadine group had improvement or resolution of abdominal pain compared with 35.7% in the placebo group (p = 0.003) [56]. These results need to be confirmed with additional larger trials. (Submitted by @JaredVerax) [Message date: March 2021, Submitted: Jan 2025]

### Source 8 — IdeaLabs Forum Q&A — Cyproheptadine

Georgi Dinkov · Forum Q&A · Dec 17, 2016

> **DennisX:** (2017-01-04) If you have BPH then cypro it is not recommended for use by most drug sites. I haven't found any negative information about metergoline and BPH or prostate cancer.
>
> **Georgi Dinkov:** (2017-01-04) Not sure I see a good reason to avoid cypro due to BPH. What is the proposed mechanism through cypro will hurt the prostate?
>
> **DennisX:** (2017-01-04) A google search of " cyproheptadine and prostate" does not return any negative pubmed studies. But when you look at drugs.com and others you find this: Do NOT use cyproheptadine if: ......... you have narrow-angle glaucoma; a peptic ulcer; an enlarged prostate; or bladder, stomach, or bowel blockage ........... Perhaps drug.com and others are just listing the drug manufacturers list of low percentage side effects?
>
> **Georgi Dinkov:** (2017-01-04) Cyproheptadine is known to cause urine retention in high doses due to its anticholinergic effects. Combine with an enlarged prostate this may cause too much retention. At least this is my guess. I don't see anything in its known effects to make it bad for prostate. The warning about peptic ulcers also does not make much sense. Cypro is a histamine antagonist that can block H2 in higher doses and H2 antagonists are used to treat peptic ulcers. So, drugs.com probably just copied something over from somebody else, who copied it from somebody else, etc, etc and eventually nobody knows who said it first and why.

### Source 9 — Ray Peat Email Advice Depository — Post 879

Ray Peat · Email · Dec 5, 2022

> ## Thread 4
>
> **Question:** I saw a study that said cyproheptadine was more effective than benzodiazepine drugs. Have you heard of anyone using it for insomnia? Or is there anything good to use for insomnia, besides benadryl? I have been trying sugar, T3, T4, beandryl, aspirin, and magnesium.
>
> **Ray Peat:** It works extremely well, but it's important to start with a much smaller dose than is usually recommended, 1 mg, or even less, can be effective, and 4 mg sometimes makes people goofy the next day. I know people who use it for nocturnal episodes of asthma or epilepsy-like episodes.
>
> **Question:** Is there a preferred brand or source for cyproheptadine?
>
> **Ray Peat:** I had some that a doctor got in a US drugstore that was good, but I don't know the brand; I got some from a drugstore in India that tasted odd and didn't seem as effective.
>
> **Question:** I took cyproheptadine last night. It was from an online pharmacy, maybe from India. It put me to sleep like benadryl. There was a period of morning grogginess today, but it feels preferable to benadryl, which makes me depressed. I also feel relaxed and less anxious. Is cyproheptadine OK to use everyday, or will it eventually cause problems?

### Source 10 — Ray Peat Email Advice Depository — Post 135

Ray Peat · Email · Feb 16, 2014

> [High serotonin and Cyproheptadine]
>
> **Question:** I have had my blood serotonin tested just before Christmas and the level was 1220 nmol/l (results said "marginally high"). My Dr didn't mention anything about it. I also had my 5-HIAA tested a few years back via an organics acid test. It was high also but I didn't worry about it at the time because I was taking 5 HTP. I emailed Dr Peat about and this is his reply:
>
> **Ray Peat:** It's important to know how it was measured, and what your platelet count was. Is your intestine inflamed? Since serotonin affects bone metabolism, have your serum calcium, phosphate, parathyroid hormone, vitamin D3, prolactin, and cortisol been measured?
>
> **Question:** I then sent him my other lab results (cholesterol, T3 Vit D, Vit A, Lactic acid, prolactin, parathyroid, etc.) I then asked him if I should see my Dr re a carcinoid tumour and this was his response:
>
> **Ray Peat:** I don't think doctors know what to do for regulating serotonin. Vitamin B6 helps to direct tryptophan toward niacinamide, away from serotonin. Gelatin contains no tryptophan, so things like consomme can be helpful. Raw carrots, because of their antiseptic effect, help to lower irritation and bloating. Antibiotics can be helpful, when the small intestine is overgrown with bacteria. Thyroid supplementation will lower cholesterol. Some people get very sleepy with just two milligrams of Periactin, so I think it's good to start with one mg. the first night. Two milligrams can make a big difference, and when symptoms stop the effects can last for days without using it.

_Generated 2026-07-20 from the Bioenergetic Oracle corpus._